Pragmatic Free Trial Meta
Pragmatic Free Trail Meta is an open data platform that enables research into pragmatic trials. 프라그마틱 플레이 collects and distributes cleaned trial data, ratings, and evaluations using PRECIS-2. This allows for a variety of meta-epidemiological studies to evaluate the effects of treatment across trials with different levels of pragmatism.
Background
Pragmatic trials are increasingly acknowledged as providing evidence from the real world to support clinical decision-making. The term "pragmatic", however, is used inconsistently and its definition and evaluation require clarification. Pragmatic trials should be designed to inform policy and clinical practice decisions, rather than to prove the validity of a clinical or physiological hypothesis. A pragmatic study should strive to be as close as is possible to real-world clinical practices that include recruiting participants, setting, designing, delivery and implementation of interventions, determination and analysis outcomes, and primary analysis. 프라그마틱 플레이 is a major difference between explanatory trials as described by Schwartz & Lellouch1, which are designed to confirm the hypothesis in a more thorough way.
Truly pragmatic trials should not conceal participants or clinicians. This can result in a bias in the estimates of the effects of treatment. Practical trials also involve patients from various health care settings to ensure that their results can be applied to the real world.
Finally studies that are pragmatic should focus on outcomes that are vital to patients, such as quality of life or functional recovery. This is particularly important for trials involving surgical procedures that are invasive or have potential serious adverse events. The CRASH trial29, for example was focused on functional outcomes to compare a 2-page case-report with an electronic system for monitoring of patients admitted to hospitals with chronic heart failure, and the catheter trial28 focused on urinary tract infections that are symptomatic of catheters as the primary outcome.
In addition to these features pragmatic trials should reduce the trial procedures and data collection requirements to reduce costs. Additionally pragmatic trials should strive to make their results as applicable to real-world clinical practice as possible by making sure that their primary method of analysis is the intention-to-treat approach (as described in CONSORT extensions for pragmatic trials).
Many RCTs that do not meet the criteria for pragmatism, however, they have characteristics that are in opposition to pragmatism, have been published in journals of varying types and incorrectly labeled pragmatic. This can result in misleading claims of pragmaticity, and the use of the term should be standardized. The creation of a PRECIS-2 tool that provides an objective, standardized evaluation of the pragmatic characteristics is a first step.
Methods
In a pragmatic trial it is the intention to inform policy or clinical decisions by demonstrating how the intervention can be incorporated into real-world routine care. This is distinct from explanation trials, which test hypotheses about the causal-effect relationship in idealized situations. Consequently, pragmatic trials may have less internal validity than explanatory trials and may be more susceptible to bias in their design, conduct and analysis. Despite these limitations, pragmatic trials can be a valuable source of information for decision-making in healthcare.
The PRECIS-2 tool assesses the level of pragmatism that is present in an RCT by assessing it across 9 domains, ranging from 1 (very explicit) to 5 (very pragmatic). In this study the areas of recruitment, organization as well as flexibility in delivery flexible adherence, and follow-up scored high. However, the principal outcome and the method of missing data was scored below the pragmatic limit. This suggests that a trial can be designed with effective practical features, yet not harming the quality of the trial.
It is difficult to determine the degree of pragmatism in a particular study because pragmatism is not a have a single attribute. Some aspects of a study can be more pragmatic than other. Furthermore, logistical or protocol modifications made during a trial can change its score in pragmatism. In addition 36% of the 89 pragmatic trials discovered by Koppenaal et al were placebo-controlled, or conducted prior to licensing, and the majority were single-center. They aren't in line with the norm and can only be referred to as pragmatic if their sponsors agree that these trials aren't blinded.
Another common aspect of pragmatic trials is that the researchers try to make their results more relevant by analyzing subgroups of the trial sample. This can result in unbalanced analyses that have lower statistical power. This increases the chance of omitting or misinterpreting differences in the primary outcomes. In the case of the pragmatic studies that were included in this meta-analysis this was a serious issue because the secondary outcomes were not adjusted for the differences in baseline covariates.
In addition practical trials can be a challenge in the gathering and interpretation of safety data. This is due to the fact that adverse events are typically reported by participants themselves and are susceptible to reporting delays, inaccuracies, or coding variations. It is therefore important to enhance the quality of outcomes ascertainment in these trials, in particular by using national registries instead of relying on participants to report adverse events on a trial's own database.
Results
While the definition of pragmatism does not mean that trials must be 100% pragmatic, there are benefits to including pragmatic components in clinical trials. These include:
Increasing sensitivity to real-world issues which reduces study size and cost and allowing the study results to be faster implemented into clinical practice (by including routine patients). However, pragmatic trials may be a challenge. The right amount of heterogeneity, like could help a study extend its findings to different patients or settings. However, the wrong type can decrease the sensitivity of the test, and therefore decrease the ability of a study to detect even minor effects of treatment.
A number of studies have attempted to categorize pragmatic trials using various definitions and scoring systems. Schwartz and Lellouch1 have developed a framework that can discern between explanation-based studies that support the physiological hypothesis or clinical hypothesis, and pragmatic studies that help inform the selection of appropriate therapies in real world clinical practice. The framework was comprised of nine domains evaluated on a scale of 1-5 with 1 being more explanatory while 5 being more pragmatic. The domains included recruitment of intervention, setting up, delivery of intervention, flex adherence and primary analysis.
프라그마틱 플레이 tool3 was built on the same scale and domains. Koppenaal et al10 created an adaptation to this assessment, dubbed the Pragmascope that was simpler to use in systematic reviews. They discovered that pragmatic systematic reviews had higher average scores in the majority of domains, with lower scores in the primary analysis domain.
This difference in the primary analysis domain could be explained by the fact that the majority of pragmatic trials process their data in the intention to treat way while some explanation trials do not. The overall score was lower for pragmatic systematic reviews when the domains of organisation, flexible delivery and follow-up were combined.
It is important to remember that a pragmatic trial doesn't necessarily mean a poor quality trial, and indeed there is an increasing rate of clinical trials (as defined by MEDLINE search, but this is neither sensitive nor specific) that use the term 'pragmatic' in their abstracts or titles. These terms may signal a greater appreciation of pragmatism in abstracts and titles, but it's unclear if this is reflected in content.
Conclusions
In recent years, pragmatic trials are gaining popularity in research as the importance of real-world evidence is becoming increasingly acknowledged. They are clinical trials randomized that compare real-world care alternatives rather than experimental treatments under development. They include patient populations that more closely mirror the patients who receive routine medical care, they utilize comparisons that are commonplace in practice (e.g. existing medications), and they depend on participants' self-reports of outcomes. This method is able to overcome the limitations of observational research, like the biases that come with the reliance on volunteers, as well as the insufficient availability and codes that vary in national registers.
Other advantages of pragmatic trials include the ability to utilize existing data sources, as well as a higher chance of detecting meaningful changes than traditional trials. However, they may still have limitations that undermine their reliability and generalizability. For example, participation rates in some trials may be lower than anticipated due to the healthy-volunteer effect and incentives to pay or compete for participants from other research studies (e.g., industry trials). The need to recruit individuals quickly restricts the sample size and the impact of many practical trials. Practical trials aren't always equipped with controls to ensure that observed variations aren't due to biases in the trial.
The authors of the Pragmatic Free Trial Meta identified 48 RCTs that self-labeled themselves as pragmatist and published from 2022. The PRECIS-2 tool was used to determine pragmatism. It includes areas such as eligibility criteria, recruitment flexibility as well as adherence to interventions and follow-up. They discovered that 14 of these trials scored highly or pragmatic sensible (i.e., scoring 5 or more) in one or more of these domains and that the majority of these were single-center.
Studies with high pragmatism scores tend to have broader criteria for eligibility than traditional RCTs. They also include populations from various hospitals. According to the authors, can make pragmatic trials more useful and applicable in everyday practice. However, they cannot ensure that a study is free of bias. Furthermore, the pragmatism of a trial is not a definite characteristic A pragmatic trial that does not possess all the characteristics of an explanatory trial can produce valuable and reliable results.